No simple method has previously been successful for preparation of C1 inhibitor. Efforts to purify the C1 esterase inhibitor have now been successful and have allowed the preparation of a fully functional molecule with twice the activity/mg of serum C1 inhibitor. Four molecules of this inhibitor inhibit one molecule of activated C1. A new purification procedure uses Zn++ chelate chromatography, never before used to prepare this protein. The plan is to perform turnover studies in man with this material. Immunoregulatory defects have been defined in Hereditary Angioedema. These patients have major autoimmune manifestations on serologic testing. They have few signs of severe clinical autoimmunity, although they have frequent mild signs, such as Sicca Syndrome, granulomatous bowel disorders, etc. The basis for this immunoregulatory defect is being investigated at present. Studies of PNH continue. It has been shown for the first time that these patients have an abnormality of the primitive erythroid stem cells (BFUE), probably as a result of stem cell complement sensitivity and resulting lysis of these cells. Unlike almost all other hemolytic states, which affect cells later in development (CFU-E), these early cells are turning over rapidly in PNH and are presumably susceptible to destruction. This may explain the propensity to an aplastic peripheral blood picture in this patient group. We have demonstrated that peripheral blood monocytes express a receptor for the complement fragment iC3b when they differentiate following attachment to glass or plastic surfaces. Efforts are underway to define the functional significance of this receptor in terms of their contribution to the host defense process. Particular attention at present is paid to their function in promoting phagocytosis.